The Ia alloantigens are the only isolated gene products of the immune response control region (I region) of the mouse major histocompatibility complex (MHC). The molecules bearing Ia alloantigenic determinants have been directly implicated in the control of immune response function by experiments showing that anti-Ia alloantisera inhibit such functions. Since Ia antigens may have an active role in the control of the immune response, these molecules must be analyzed to see if their structural features can explain how they carry out their proposed function. The research proposed here includes structural analysis and serological investigation of Ia molecules. Structural analysis will include elucidation of native secondary structure involving two glycopolypeptide chains, assessment of variability in primary structure by peptide mapping, localization of antigenic sites, and attempts to determine whether non-MHC genes determine parts of the Ia molecules. Serological investigations will utilize immune precipitation by alloantisera as a screening tool for analysis of Ia polymorphism and as an auxiliary mapping technique to gather information about the genetic organization of the I region.